Is OCRL p.Arg35= (c.105G>A) pathogenic?

OCRL p.Arg35= (c.105G>A) is classified Benign/Likely benign in OCRL (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-09). Ultra-rare (popmax 0.0272%, nfe); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with OCRL p.Arg35= (c.105G>A)?

OCRL p.Arg35= (c.105G>A) is associated with Nephrolithiasis/nephrocalcinosis, Dent disease type 2, oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Arg35= (c.105G>A) in the general population?

OCRL p.Arg35= (c.105G>A) is ultra-rare (popmax 0.0272%, nfe) (gnomAD).

OCRL p.Arg35=

c.105G>A · rs142321728 · VCV588729

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0272%, nfe)

Conditions

Nephrolithiasis/nephrocalcinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.4	GERP 0.73, phastCons 1
Overall
CADD	13.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0272% European (non-Finnish) · 242/890,296 alleles

Filtering AF 0.0243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0232%

Overall 0.0211% 254/1,204,759 alleles · ultra-rare exomes 233/1,092,890 · genomes 21/111,869 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0272%	3,679
Remaining individualsnot grpmax-eligible	0.0126%	7,906
African / African-American	0.0105%	9,519

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: OCRL
Protein: p.Arg35=
Coding: c.105G>A
MANE Select: NM_000276
dbSNP: rs142321728
Type: single nucleotide variant
Location: chrX:129540809 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 35: the ph domain; a β-strand

Full OCRL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Nephrolithiasis/nephrocalcinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Dent disease type 2 oculocerebrorenal syndrome

Similar variants

OCRL c.1244+1G>A Pathogenic/Likely pathogenic ★★ same condition
OCRL c.1714-1G>A Pathogenic ★★ same condition
OCRL c.2256+1G>T Likely pathogenic ★★ same condition
OCRL c.560+1G>C Pathogenic/Likely pathogenic ★★ same condition
OCRL c.940-11G>A Pathogenic/Likely pathogenic ★★ same condition
OCRL p.Ala861Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
OCRL p.Arg318Cys Pathogenic/Likely pathogenic ★★ same condition
OCRL p.Arg318His Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ocrl-p-arg35 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown